No pharmaceutical opinion available for this interaction.
Darunavir / cobicistat can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Rifabutin.
Rifabutin can induce the metabolism (CYP 3A4) and decrease the plasma concentration of Darunavir / cobicistat.
3A4 (major) and 2D6 (minor)
3A4 (potent) and 2D6 (weak), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3.
Possible decrease of clinical efficacy.
Risk of a possible development of resistance to antiretroviral class.
Association not recommended. If used, closely monitor clinical effectiveness.
Choose an alternative.
Protease inhibitor boosted with ritonavir or dolutegravir 50 mg QD or raltegravir 400 mg BID or raltegravir HD 1200 mg QD : see dolutegravir + rifabutin or raltegravir + rifabutin.
3A4, cholibestérase, Un des métabolites est métabolisé CYP 3A4 (25-O-desacetyl rifabutine = activité similaire à la rifabutine)
Possible increase of adverse effects.
Avoid this combination, otherwise a decrease in the dose is necessary.
Dose reduction suggested of up to 75% (e.g., 150 mg every other day).
Monitor closely clinical efficacy and appearance of adverse effects.
Rifabutin adverse effects : rash, taste alterations, anorexia, nausea, insomnia, facial paralysis, twitching, peripheral neuritis, neutropenia, thrombocytopenia, arthralgia, uveitis, elevation of liver function tests.
Darunavir plasma level
Viral load HIV
Several studies were initially done with healthy subjects with the combination of protease inhibitors and rifabutin. These studies demonstrated that a dose of rifabutin 150 mg 3 times/week associated with protease inhibitors was approximately equivalent to a dose of rifabutin 300 mg QD.
Subsequently, studies in subjects co-infected with HIV and tuberculosis demonstrated that the dose of 150 mg 3 times/week was insufficient for some subjects.
Ref #3117 : To optimize the monitoring for rifabutin, dosage of this agent, at equilibrium (t1/2 normal; 25hrs), may be necessary. The targeted therapeutic index of 0.3-0.9μg/ml 3-4 post dose (Cmax) and a dose reduction may be necessary from 1 μg/ml depending on the clinical context.